CN109793745B - Application of aspirin in preparation of medicine for treating dyskinesia and pharmaceutical composition thereof - Google Patents
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Abstract
The scheme discloses application of aspirin in the technical field of medicines in preparation of medicines for preventing or treating levodopa-induced dyskinesia and a pharmaceutical composition thereof. The pharmaceutical composition takes aspirin as an active ingredient, and is prepared into tablets, capsules, granules, pills, dripping pills, syrups, powders, suppositories, drops, emulsions, injections, solutions or suspensions by adding a pharmaceutical carrier or excipient. The aspirin is pioneering to be applied to the treatment of the L-dopa induced dyskinesia after long-term administration, so that the aspirin has a certain treatment effect on symptoms of the Parkinson's disease, can delay or improve the effect of the L-dopa induced dyskinesia after long-term administration to a greater extent, reduces the side effect of the dyskinesia caused by the administration of drugs in the treatment process of the Parkinson's disease, and plays a synergistic effect of a single compound and the drugs to treat the Parkinson's disease. Therefore, the utility model is suitable for clinical application.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of aspirin in preparation of a medicine for treating dyskinesia and a pharmaceutical composition of aspirin.
Background
Parkinson's Disease (PD) is a nervous system degenerative disease with progressive loss, degeneration and death of dopaminergic neurons in the substantia nigra pars compacta of the midbrain as a main pathological feature, and is frequently seen in middle-aged and elderly people. Its typical clinical manifestations are resting tremor, muscle rigidity, bradykinesia, postural instability, etc. PD is second only to alzheimer's disease, causing neuro-degeneration in the middle aged and elderly, and places a heavy burden on society and families. At present, the pathogenesis of PD is unclear, and the current treatment status is obviously limited due to poor curative effect or side effect. Therefore, finding effective treatment schemes and drugs to alleviate symptoms in PD patients is of great clinical significance.
Levodopa (L-DOPA) is still the gold standard in PD therapeutic drugs at present, is the metabolic precursor of Dopamine (DA), can enter basal ganglia through a blood brain barrier and then is decarboxylated to form dopamine, and plays a role in supplementing dopamine neurotransmitter deficiency. The levodopa can effectively improve the akinesia and the rigor state, and is commonly used for clinical combined treatment of compound levodopa or levodopa and other auxiliary medicaments. However, after 2 to 5 years of treatment with levodopa, more than half of the cases begin to exhibit fluctuation in drug efficacy. The duration of symptom improvement after each administration is shorter and shorter, and the phenomenon of hyperactivity additionally occurs, so that patients often swing back and forth between serious motion deficiency and uncontrollable hyperactivity, which is called as the dyskinesia.
LID (Levodopa-induced dyskinesia) is one of the most common complications of the long-term treatment of PD by Levodopa, mainly manifested by chorea and athetosis, and the adverse reactions seriously affect the treatment and daily life quality of PD patients. The progressive dopamine neuron loss of the nigrostriatal and the exogenous supplement of the L-DOPA are closely related to the LID, the pathogenesis of the LID is still not completely clear at present, the researches are all mechanism researches before clinic, and no LID treatment method or medicament exists in clinic at present, so that the LID prevention and treatment of PD patients still need to be solved, and a potential synergistic action strategy is combined with levodopa to possibly provide new adjuvant therapy for the Parkinson's disease.
Aspirin (Aspirin, ASA acetylsalicylic acid) is a white crystal or crystalline powder, odorless or slightly smelly with acetic acid, slightly soluble in water, readily soluble in ethanol, soluble in ether and chloroform, and acidic in aqueous solution. It has good effect in relieving mild or moderate pain, such as toothache, headache, neuralgia, muscular soreness and dysmenorrhea, and can be used for treating fever due to common cold and influenza, and rheumatalgia. In recent years, aspirin has an inhibiting effect on platelet aggregation and can prevent thrombosis, and the aspirin is clinically used for preventing transient ischemic attack, myocardial infarction, artificial heart valves and venous fistula or the formation of thrombosis after other operations. In the prior art, no report about the application of aspirin in preparing a medicine for treating the dyskinesia exists.
Disclosure of Invention
In order to solve the defects of the prior art, the invention provides the application of aspirin in the aspect of treating the dyskinesia, the application of aspirin in preparing a medicine for treating the dyskinesia and a pharmaceutical composition thereof.
The application of aspirin in the scheme in the preparation of the medicine for treating the dyskinesia refers to the application of aspirin in the preparation of the medicine for preventing or treating the levodopa-induced dyskinesia.
The aspirin is used as an active ingredient in the preparation of a medicine for treating the transaction symptom, and the medicine is prepared by adding a medicinal carrier or an excipient into the aspirin.
In the application of the aspirin in preparing the medicine for treating the dyskinesia, the medicine comprises the following raw materials in parts by weight: 10-400 parts of aspirin, 0.1-0.4 part of magnesium stearate, 4-12 parts of sodium carboxymethyl starch and 50-100 parts of microcrystalline cellulose. Mixing aspirin, sodium carboxymethyl starch and microcrystalline cellulose, sieving, mixing, adding appropriate amount of water or ethanol, granulating, drying, grading, adding magnesium stearate, and tabletting with a punching device to obtain medicinal tablet for preventing or treating levodopa induced dyskinesia.
The aspirin is applied to the preparation of the medicine for treating the dyskinesia, and the medicine comprises the following raw materials in parts by weight: 50-400 parts of aspirin, 0.1-0.3 part of magnesium stearate, 4-12 parts of sodium carboxymethyl starch and 50-100 parts of starch. The aspirin, the sodium carboxymethyl starch and the starch are uniformly mixed, a proper amount of ethanol is added for granulation, drying and granulation are carried out, the magnesium stearate is added, and then the mixture is filled into a gelatin capsule, so that the medicine capsule for preventing or treating the levodopa induced dyskinesia can be obtained.
The aspirin is applied to the preparation of the medicine for treating the dyskinesia, and the medicine comprises the following raw materials in parts by weight: 1-10 parts of aspirin and 1-10 parts of a flavoring agent, wherein the flavoring agent is dextrin or sucrose. Mixing aspirin and sucrose/dextrin uniformly, adding appropriate amount of water or ethanol to make into soft mass, sieving, granulating, drying, grading, and packaging to obtain medicinal granule for preventing or treating levodopa induced dyskinesia.
The aspirin is applied to the preparation of the medicine for treating the dyskinesia, and the medicine comprises the following raw materials in parts by weight: 10-400 parts of aspirin, 100-400 parts of polyethanol or soybean oil, 3-10 parts of a suspending agent, 3-10 parts of an emulsifier, 50-100 parts of gelatin, 10-20 parts of glycerol and 50-100 parts of purified water. Putting gelatin into a gelatin dissolving tank, adding purified water, heating at 70 ℃ to dissolve, adding glycerol, stirring uniformly, removing bubbles under vacuum, keeping the temperature and standing, uniformly mixing aspirin, polyethanol/soybean oil, an emulsifier and a suspending agent according to a proportion, putting the mixture and the prepared gelatin into a rotary capsule press, pressing into soft capsules, shaping and drying to obtain the medicinal soft capsules for preventing or treating levodopa-induced dyskinesia. In order to prolong the storage time of the medicine, a proper amount of preservative can be added in the preparation stage to prolong the shelf life of the medicine.
The aspirin is applied to the preparation of a medicine for treating the transaction symptoms, and the medicine comprises, by weight, 1-10 parts of aspirin and 20-40 parts of a matrix, wherein the matrix is at least one of polyethylene glycol, polyvinylpyrrolidone, stearic acid and glyceryl monostearate. Adding water into aspirin, making into uniform paste, adding molten matrix solution, heating and melting to obtain clear liquid, adding into preheated dripping pill machine, controlling dripping temperature and speed, dripping into condensate, making into pill, sucking off the condensate, collecting dripping pill, and placing into dryer to obtain the medicinal dripping pill for preventing or treating levodopa induced dyskinesia. In order to improve the roundness of the dripping pill, methyl silicone oil can be used as condensate.
The aspirin is applied to the preparation of the medicine for treating the dyskinesia, and the medicine comprises the following raw materials in parts by weight: 1-20 parts of aspirin, 1.5 parts of sodium carboxymethyl cellulose, 0.1 part of saccharin sodium and 100 parts of purified water. Dispersing sodium carboxymethyl cellulose in hot water, cooling, mixing with water suspension containing aspirin and saccharin sodium, blending the solution into required volume, mixing uniformly, sterilizing, and packaging to obtain the medicinal syrup for preventing or treating levodopa induced dyskinesia. In order to improve the taste of the medicine, a flavoring agent can be added according to the actual situation; in order to increase the shelf life of the drug, a suitable amount of preservative may be added.
In another aspect, the present invention provides a pharmaceutical composition comprising aspirin as an active ingredient, in combination with a pharmaceutically acceptable carrier or excipient, for preventing or treating levodopa-induced dyskinesia.
Preferably, the pharmaceutical composition is prepared into tablets, capsules, granules, pills, drop pills, syrups, powders, suppositories, drops, emulsions, injections, solutions or suspensions.
Preferably, the pharmaceutical composition is prepared into tablets, soft capsules, hard capsules, granules, pills, dripping pills or syrups.
The invention has the beneficial effects that: the invention pioneers the aspirin in the treatment of the L-dopa induced dyskinesia after long-term administration, has a certain treatment effect on the symptoms of the Parkinson's disease, can delay or improve the effect of the L-dopa induced dyskinesia after long-term administration to a greater extent, reduces the side effect of the dyskinesia caused by the administration of drugs in the Parkinson's treatment process, and plays a synergistic effect of a single compound and the drugs to treat the Parkinson's disease. Therefore, the utility model is suitable for clinical application.
Drawings
FIG. 1 is a graph of the effect of aspirin on the oral facial AIM score in levodopa-induced dyskinesia rats;
FIG. 2 is a graph of the effect of aspirin on the upper limb AIM score of levodopa-induced dyskinesia rats;
FIG. 3 is a graph of the effect of aspirin on levodopa-induced dyskinesia rat axial AIM score;
FIG. 4 is a graph of the effect of aspirin on total AIM score in levodopa-induced dyskinesia rats;
FIG. 5 is a graph of the effect of aspirin on the locomotor ability of levodopa-induced dyskinesia rats;
FIG. 6 is a graph showing the effect of aspirin on Levodopa-induced dyskinesia rat inflammatory factors.
Detailed Description
The following is further detailed by way of specific embodiments:
the reference numerals in the drawings of the specification have the meanings given below: m represents 6-OHDA (6-hydroxydopa); ASA stands for aspirin, L-DOPA for levodopa; # denotes P <0.05 in comparison to group M in three other groups; ω represents three additional groups compared to the M + ASA group: Ψ represents three additional groups compared to the M + L-DOPA group: p is less than 0.05.
Example 1
The preparation method of the medicinal tablet for preventing or treating the levodopa-induced dyskinesia comprises the following steps: taking 10-400 mg of aspirin, 0.1-0.40 mg of magnesium stearate, 4-12 mg of sodium carboxymethyl starch, 50-100 mg of microcrystalline cellulose, mixing the aspirin, the sodium carboxymethyl starch and the microcrystalline cellulose, sieving, uniformly mixing, adding a proper amount of water or ethanol for granulation, drying, granulating, adding the magnesium stearate, and pressing the granules into tablets by using a punching device to obtain the aspirin tablet. The dosage is as follows: the dosage is 5-50mg/kg based on aspirin active ingredient. In this example, 193 mg of aspirin, 0.15 mg of magnesium stearate, 5.8 mg of sodium carboxymethyl starch, and 63 mg of microcrystalline cellulose were selected.
Example 2
The preparation method of the medicine capsule for preventing or treating the levodopa-induced dyskinesia comprises the following steps: taking 50-400 mg of aspirin, 0.1-0.30 mg of magnesium stearate, 4-12 mg of sodium carboxymethyl starch and 50-100 mg of starch, uniformly mixing the aspirin, the sodium carboxymethyl starch and the starch, adding a proper amount of ethanol for granulation, drying, granulating, adding the magnesium stearate, and filling into gelatin capsules to obtain the aspirin-modified starch. The dosage is as follows: the dosage is 5-50mg/kg based on aspirin active ingredient. In this example, 326 mg of aspirin, 0.21 mg of magnesium stearate, 5mg of sodium carboxymethyl starch, and 86 mg of starch were selected.
Example 3
The preparation method of the medicinal granules for preventing or treating the levodopa-induced dyskinesia comprises the following steps: taking 1-10 g of aspirin, 1-10 g of dextrin or sucrose, and a proper amount of a flavoring agent and a sweetening agent, uniformly mixing the aspirin, the sucrose/dextrin, the flavoring agent and the sweetening agent, adding a proper amount of water or ethanol to prepare a soft material, sieving and granulating, drying, finishing granules, and subpackaging to obtain the aspirin-modified aspirin soft capsule. The dosage is as follows: the dosage is 5-50mg/kg based on aspirin active ingredient. In this example, 6.8 g of aspirin, 3.6 g of dextrin or sucrose, and appropriate amounts of flavoring agent and sweetener are selected.
Example 4
A preparation method of a medicinal soft capsule for preventing or treating levodopa-induced dyskinesia comprises the following steps of taking 10-400 mg of aspirin, 100-400 mg of polyethanol or soybean oil, 3-10 mg of a suspending agent, 3-10 mg of an emulsifier, 50-100 mg of gelatin, 10-20 mg of glycerol, 50-100 mg of purified water and a proper amount of a preservative, placing the gelatin in a gelatin dissolving tank, adding purified water, heating at 70 ℃ to dissolve, adding the glycerol and the preservative, stirring uniformly, removing bubbles in vacuum, keeping the temperature and standing, mixing the aspirin, the polyethanol/soybean oil, the emulsifier and the suspending agent uniformly according to a proportion, placing the mixture and the prepared gelatin in a rotary capsule press, pressing into soft capsules, shaping, and drying to obtain the levodopa-induced dyskinesia soft capsule. The dosage is as follows: the dosage is 5-50mg/kg based on aspirin active ingredient. In this example, 269 mg of aspirin, 251 mg of polyethanol or soybean oil, 5mg of suspending agent, 4 mg of emulsifier, 79 mg of gelatin, 13 mg of glycerol, 85 mg of purified water and an appropriate amount of preservative were selected.
Example 5
A preparation method of a medicinal dripping pill for preventing or treating levodopa-induced dyskinesia comprises the following steps of taking 1-10 mg of aspirin, 20-40 mg of a matrix and a proper amount of methyl silicone oil, adding water into the aspirin to prepare uniform paste, adding a molten matrix solution, heating and melting to obtain a clear liquid, pouring the clear liquid into a preheated dripping pill device, controlling the dripping temperature and speed, dripping the clear liquid into a methyl silicone oil condensate, forming pills, sucking the condensate, collecting the dripping pills, and placing the dripping pills into a dryer to obtain the dripping pills. The dosage is as follows: the dosage is 5-50mg/kg based on aspirin active ingredient. In this example, 8.6 mg of aspirin, 32 mg of a substrate and an appropriate amount of methylsilicone oil were selected.
Example 6
A preparation method of a medicinal syrup for preventing or treating levodopa-induced dyskinesia comprises the following steps of taking 1-20 g of aspirin, 1.5 g of sodium carboxymethyl cellulose, 0.1 g of saccharin sodium, a proper amount of a flavoring agent, a proper amount of a preservative and 100 ml of purified water, dispersing the sodium carboxymethyl cellulose in hot water, cooling, mixing with an aqueous suspension containing the aspirin, the saccharin sodium, the flavoring agent and the preservative, blending the solution into a required volume, uniformly mixing, sterilizing and subpackaging to obtain the levodopa-induced dyskinesia syrup. The dosage is as follows: the dosage is 5-50mg/kg based on aspirin active ingredient. In this example, 16.3 g of aspirin, 1.5 g of sodium carboxymethyl cellulose, 0.1 g of saccharin sodium, a proper amount of flavoring agent, a proper amount of preservative, and 100 ml of purified water are selected.
In order to ensure the science, the reasonability and the effectiveness of the technical scheme of the invention, the inventor carries out a series of experiments.
Experimental materials and instruments
1.1 Experimental animals
SD male rats, with a weight of 200-.
1.2 Main instrumentation
Rat brain stereotaxic apparatus (Narishige, USA), OLYMPUS optical microscope (OLYMPUS, Japan), BSS-110 electronic analytical balance (electronic balance, Inc. Sadolis, Beijing), Milli QA pure water processor (Millipore, Inc.), etc.
1.3 Main test reagents
Aspirin with purity greater than or equal to 98% (Sigma company); levodopa with purity not less than 98 percent (Sigma company), BCA kit, RIPA lysate, beta-actin mouse anti-rat polyclonal antibody, COX-2, IL-6 and iNOS polyclonal antibody.
Second, Experimental methods
2.1 Experimental groups
30 SD rats, male, with a weight of 200- & lt250 g, were randomly divided into 5 groups of 6 rats each, set as: blank group, 6-OHDA (6-OHDA, 8 μ g) group, 6-OHDA + levodopa (L-DOPA, 25mg/kg) group, 6-OHDA + ASA (aspirin, 10mg/kg) group, 6-OHDA + L-DOPA (25mg/kg) + aspirin (10mg/kg) group. After 21 days of molding, ASA is administered by gavage and L-DOPA is injected intraperitoneally for 21 days.
2.2 preparation of animal models
SD rats were anesthetized with 7% chloral hydrate (0.5mL/100g) under sterile conditions with bregma as the origin of coordinates, bregma 5.2mm posterior, midline 2.2mm, subdural 8.0mm, and 4. mu.L of 6-OHDA at 2. mu.g/. mu.L concentration injected at a constant rate.
2.3 behavioral experiments
2.3.1 AIM score
Rats were subjected to AIM scoring on days 7, 14, 21 and evaluated every 30min for 4 times at 120min after dosing. And A IM scoring: the evaluation was carried out in 4 parts (upper arm AIM, orofacial AIM and axial AIM), each part was graded by 5 (0-4) according to the presence or absence and severity: theoretically, the maximum mean integral of 1 rat after 1 administration is 16 points. 0: none; 1: 50% of the time of no observation for the presence of AIM; 2: AIM presence greater than 50% of observation time; 3: persisting, stopping the stimulation; 4: persisting, the stimulus cannot stop it.
2.3.2 step by step experiments
Rat forelimb motor function was measured before and 30min after each levodopa treatment: the experimenter fixes the back half part and hind limb of the rat body with one hand to lift the ground, fixes the forelimb on one side with the other hand to land the other forelimb, moves the rat with the direction of the rat's forehand inclined to one side (moving 90cm in 5 s), records the number of the forelimb contact and lift-off steps on the land side of the rat when moving, and alternately measures the number of the steps of the forelimbs on both sides
2.4 taking materials
After the rats in each group are respectively narcotized with 7% chloral hydrate, the abdominal cavity is opened, the abdominal aorta is clamped, the thoracic cavity is cut open, the heart is fully exposed, the transirrigation needle is inserted into the aorta through the apex cordis, the right auricle is fixed and cut open by hemostatic forceps, 0.1mol/L PBS liquid is perfused at a certain speed until the blood in the brain is washed clean, the head is directly cut off, the brain is taken out, and the midbrain is separated and stored at the temperature of minus 80 ℃.
2.5 protein assay
1) Protein extraction: taking out the midbrain, adding appropriate amount of prepared RIPA lysate, grinding, homogenizing, standing on ice for 20min, centrifuging at 12000 rpm for 15min at 4 deg.C, collecting supernatant, and storing at-80 deg.C.
2) The BCA method detects the protein concentration of the sample.
3) Sample protein denaturation: and determining the protein quality of the sample detection according to the protein concentration and the volume of each group of samples, and calculating the detection volume of each group of samples under the condition of the same quality of protein.
4) Sample adding: and (3) taking out 10% NuPAGE gel, fixing the NuPAGE gel in an electrophoresis tank, filling electrophoresis liquid in the electrophoresis tank, vertically pulling out a comb on the gel, respectively adding the detection samples into gel holes, covering the electrophoresis tank, connecting positive and negative electrodes, and starting electrophoresis.
5) Electrophoresis: firstly, adjusting the voltage to 70V, carrying out electrophoresis for about 40min, after the Maker strip begins to be separated, adjusting the voltage to 110V until the Maker strip reaches the bottom of the lower layer gel, and stopping electrophoresis.
6) Electric conversion: performing electric transfer by using semi-dry transfer, cutting gel with required molecular weight, placing the gel into an electric transfer box according to the sequence of filter paper-polyvinylidene fluoride membrane (PVDF membrane) -gel-filter paper, setting the voltage at 25V, setting the voltage at 1.0A, and starting the electric transfer within 30 min.
7) Washing: taking out the PVDF membrane, washing with TBST once for 10min and 3 times;
8) and (3) sealing: sealing with 5% skimmed milk powder for 3 hr, washing with TBST for 10min for 3 times;
9) adding a primary antibody: incubating at 4 ℃ overnight, washing with TBST once for 10min and 3 times;
10) adding a secondary antibody: incubating for 1h at room temperature, washing with TBST for 10min once and 3 times;
11) exposing;
12) and (4) carrying out gray level calculation on the strip by adopting a Quantity One quantitative analysis software system.
2.6 statistical analysis of data
The experimental data were statistically analyzed using SPSS21.0 statistical software, all data are expressed as means. + -. standard deviation, group differences in mean were compared using one-way analysis of variance (ANOVA), group differences in mean were compared using the LSD method for all means, variance was varied, group differences in mean were compared using Dunnett's T3, and P <0.05 was statistically significant.
Third, experimental results
1. Effect of Aspirin on Levodopa-induced dyskinesia rat AIM score
The evaluation was carried out by dividing into 4 parts (upper limb AIM, orofacial AIM, axial AIM) (fig. 1-3), and the results of the total division are shown in the figure (fig. 4). The animals had increased AIM scores at various time points after L-DOPA administration compared to the 6-OHDA group, with statistical differences (P < 0.05) with increasing AIM scores at longer administration times; while ASA treatment improved AIM scores in rats to some extent, on days 1, 7, 14 and 21, there was a trend toward a decrease in AIM scores for upper limbs, orofacial AIM and axial AIM, all with statistical differences (P < 0.05). Thus, it is known that administration of aspirin improves dyskinesia caused by long-term administration of levodopa.
2. Effect of Aspirin on Levodopa-induced dyskinesia rat motility
The locomotor ability of the rats was tested by the step-by-step experiment, and as shown in fig. 5, the locomotor ability of the rats was significantly improved by administration of levodopa (P < 0.05), and the locomotor function of the rats was not improved by administration of aspirin alone, as compared with the 6-OHDA group. However, after the aspirin and the levodopa are used together, the motor function of a rat is improved, and experimental results prove that the aspirin does not influence the curative effect of the levodopa while improving the abnormal symptoms.
3. Effect of Aspirin on Levodopa-induced dyskinesia rat inflammatory factor
The occurrence of dyskinesia is closely related to the release of inflammatory factors, and the results are shown in fig. 6. Compared with rats in the M group, the rats have increased inflammatory factor expression by long-term administration of levodopa, and have statistical difference; however, after aspirin administration, the release of inflammatory factors was reduced to some extent, and there was a statistical difference compared with the M + L-DOPA group. Therefore, it is known that aspirin administration can reduce the release of inflammatory factors in rats with levodopa-induced dyskinesia.
To summarize: from the perspective of an overall experiment, the aspirin is verified to delay or treat the dyskinesia caused by long-term levodopa administration and improve the motor function by AIM scoring and other methods. Thus proving that the aspirin has a treatment effect on the dyskinesia and can delay the occurrence and the development of the dyskinesia.
The invention has the advantages that: the invention provides an application of aspirin, namely an application of aspirin in preparation of a medicine for preventing or treating levodopa-induced dyskinesia. Aspirin has effects of preventing and treating Levodopa induced dyskinesia.
(1) Aspirin can improve the AIM score of rats to a certain extent, obviously reduce oral and facial, forelimb AIM and axial AIM after administration, and can improve the dyskinesia caused by long-term administration of levodopa.
(2) The aspirin does not influence the effect of levodopa on treating PD while improving the dyskinesia.
(3) Aspirin can reduce the expression of inflammatory factors of rats with levodopa-induced dyskinesia.
Aspirin can improve the clinical symptoms of the dyskinesia and delay the appearance time of the dyskinesia. The traditional Chinese medicine composition has a certain treatment effect on symptoms of the Parkinson's disease, can delay or improve the dyskinesia induced by long-term administration of levodopa to a greater extent, reduces the dyskinesia which is a side effect caused by medicines in the Parkinson treatment process, and plays a synergistic effect of a single compound and the medicines to treat the Parkinson's disease. Is suitable for being popularized and used in clinic.
Claims (8)
1. The application of aspirin in preparing medicine for treating dyskinesia is characterized in that: the aspirin is applied to the preparation of the medicine for preventing or treating the levodopa-induced dyskinesia.
2. Use of aspirin according to claim 1 for the preparation of a medicament for the treatment of dyskinesia, wherein: the medicine is prepared by taking aspirin as an active ingredient and adding a medicinal carrier or excipient.
3. Use of aspirin according to claim 2 in the manufacture of a medicament for the treatment of dyskinesia, wherein: the medicine comprises the following raw materials in parts by weight: 10-400 parts of aspirin, 0.1-0.4 part of magnesium stearate, 4-12 parts of sodium carboxymethyl starch and 50-100 parts of microcrystalline cellulose.
4. Use of aspirin according to claim 2 in the manufacture of a medicament for the treatment of dyskinesia, wherein: the medicine comprises the following raw materials in parts by weight: 50-400 parts of aspirin, 0.1-0.3 part of magnesium stearate, 4-12 parts of sodium carboxymethyl starch and 50-100 parts of starch.
5. Use of aspirin according to claim 2 in the manufacture of a medicament for the treatment of dyskinesia, wherein: the medicine comprises the following raw materials in parts by weight: 1-10 parts of aspirin and 1-10 parts of a flavoring agent, wherein the flavoring agent is dextrin or sucrose.
6. Use of aspirin according to claim 2 in the manufacture of a medicament for the treatment of dyskinesia, wherein: the medicine comprises the following raw materials in parts by weight: 10-400 parts of aspirin, 100-400 parts of polyethanol or soybean oil, 3-10 parts of a suspending agent, 3-10 parts of an emulsifier, 50-100 parts of gelatin, 10-20 parts of glycerol and 50-100 parts of purified water.
7. Use of aspirin according to claim 2 in the manufacture of a medicament for the treatment of dyskinesia, wherein: the medicine comprises, by weight, 1-10 parts of aspirin and 20-40 parts of a matrix, wherein the matrix is at least one of polyethylene glycol, polyvinylpyrrolidone, stearic acid and glyceryl monostearate.
8. Use of aspirin according to claim 2 in the manufacture of a medicament for the treatment of dyskinesia, wherein: the medicine comprises the following raw materials in parts by weight: 1-20 parts of aspirin, 1.5 parts of sodium carboxymethyl cellulose, 0.1 part of saccharin sodium and 100 parts of purified water.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004085712A2 (en) * | 2003-03-24 | 2004-10-07 | Penn State Research Foundation | Multi-functional polymeric materials and their uses |
| CN107624067A (en) * | 2015-03-06 | 2018-01-23 | 奥斯拜客斯制药有限公司 | Method for treating Abnormal involuntary movement obstacle |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102525876B (en) * | 2010-12-15 | 2014-03-12 | 西安力邦医药科技有限责任公司 | Aspirin solid dispersion, as well as preparation method, pharmaceutical composition and use thereof |
| CN102641254B (en) * | 2012-05-07 | 2013-10-09 | 山东新华制药股份有限公司 | Preparation method of aspirin enteric-coated sustained-release preparation |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004085712A2 (en) * | 2003-03-24 | 2004-10-07 | Penn State Research Foundation | Multi-functional polymeric materials and their uses |
| US20050169882A1 (en) * | 2003-03-24 | 2005-08-04 | Lowe Tao L. | Multi-functional polymeric materials and their uses |
| CN107624067A (en) * | 2015-03-06 | 2018-01-23 | 奥斯拜客斯制药有限公司 | Method for treating Abnormal involuntary movement obstacle |
Non-Patent Citations (1)
| Title |
|---|
| 链球菌感染后风湿热和风湿性心脏病;高路等;《临床儿科杂志》;20061231;第24卷(第6期);第461-463页 * |
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